Objectives This study aimed to assess how often overridden drug allergy alerts (ODAAs) lead to allergic adverse drug events (All-ADEs) and to evaluate the frequency with which drug allergy alerts (DAAs) were overridden and the reasons, as well as appropriateness of these overrides. Methods A retrospective observational study of DAA generated between 2014 and 2016 was conducted. The corresponding DAA records were reviewed to determine the frequency of alert overrides. A chart review was performed on a subset of 194 ODAA (the first of every 3 chronologically ordered ODAA) to identify All-ADEs and to evaluate the override reasons and the appropriateness of these overrides. Results A total of 2044 DAAs were overridden (override rate of 44.8%). Most were triggered by a nonexact match (93.81%), when ordering nervous system (21.1%) and cardiovascular system (19.6%) drugs and were generated by physicians (72.7%). The main override reason was that the patient was already taking the drug or had previously tolerated the drug. Only 9.28% of ODAAs were inappropriately overridden. Six All-ADEs (3.09%) were identified and were due to anti-infective (1), antineoplastic (1), and iodinated-contrast (4) drug administration. Most All-ADEs were cutaneous and were mild. None was life-threatening or fatal. The All-ADEs rate was higher among inappropriately ODAA (15.79%, P = 0.013). Conclusions Alert overrides are not exempt from clinical consequences, although few are associated with All-ADEs. ...

The addition of a fourth year to the hospital pharmacy residency program has allowed trainees to rotate through various inpatient clinical units where they can, under the supervision of a specialist pharmacist, work shoulder to shoulder with other healthcare providers to ensure that patients receive the care they need. In addition to sharing their pharmacotherapeutic and pharmacokinetic knowledge (among others) with their colleagues, hospital pharmacists can and should contribute with their expertise in the areas of drug evaluation, selection and positioning. As no other healthcare professional masters like a pharmacist the intricacies of treatment efficacy or effectiveness, or of therapeutic safety, conveying this knowledge is yet another of the many clinical activities a hospital pharmacist must perform as a member of a multidisciplinary team, while assisting fellow-team members in deciding what medications are best suited to each patient. Both the public authorities and the pharmaceutical profession as a whole should make sure the pharmacist's role is rightfully valued and given the recognition it deserves.

Background: The proper dosage of antibiotics is a key element in the effective treatment of infection, especially in critically ill patients. This study aimed to evaluate the efficacy of optimized meropenem regimens based on pharmacokinetic/pharmacodynamic criteria in patients admitted to the intensive care unit. Methods: This observational, naturalistic, retrospective, unicentric cohort study was performed between May 2011 and December 2017. The clinical and bacteriologic responses of 77 control intensive care unit patients receiving meropenem were compared with those of 77 propensity score-balanced patients who received meropenem dose adjusted by therapeutic drug monitoring. The primary end point of clinical response was a reduction at the end of treatment of at least 80% of the maximum procalcitonin (PCT) value recorded during the meropenem treatment. Results: The primary end point was met by 55 patients (71.4%) in the adjusted group compared with 41 (53.3%) patients in the control group (mean difference 18.1%, P = 0.02). Fifty-one patients (66.2%) in the adjusted group required a meropenem dose adjustment, being necessary in 46 of them (90.2%) to decrease the dose. The reduction of PCT was the greatest in the adjusted group compared with the unadjusted group (93% versus 85%, P = 0.004); a greater percentage of patients reached a PCT level < 0.5 ng/mL (63.6% versus 41.6%, P = 0.006), and there was a trend toward an improved bacteriologic response (relative risk = 1.27; 95% confidence interval: 0.92-1.56). There were no differences in early mortality or safety between groups. Conclusions: Adjustment of meropenem therapy by monitoring is a useful strategy for improving meropenem effectiveness in the treatment of infection in critically ill patients, with no impact on safety.

En la revisión de borradores de informes para evaluación y posicionamiento de nuevos fármacos en un entorno multidisciplinar, se observan determinados errores de expresión o criterio que se repiten con frecuencia. Principalmente, están relacionados con la consideración de ¿diferencias¿ o tendencias no significativas, abuso de la reducción relativa del riesgo, errores en la valoración de resultados por subgrupos sin calcular la interacción estadística, confusiones en la interpretación de las comparaciones indirectas, sobrevaloración de la relevancia clínica con variables subclínicas y afirmaciones sesgadas en el apartado de seguridad, entre otros. También se observa a menudo ambigüedad o inhibición en el posicionamiento, especialmente en situaciones de precariedad en la evidencia disponible. El presente trabajo expone de forma sintética tales errores, aclara algunos términos comunes y propone expresiones o criterios alternativos que se consideran preferibles, con el fin de ofrecer una evaluación para la toma de decisiones en beneficio de los pacientes.

Background: Incorporating in the Intensive Care Unit (ICU) a clinical pharmacist who performs interventions on antimicrobials may be cost-effective. Objectives: To evaluate the clinical and economic impact of clinical pharmacist interventions on antimicrobials in an ICU. To identify drug related problems and medication errors detected by the pharmacist. Methods: A retrospective observational study was performed to analyze drug related problems, medication errors and clinical pharmacist interventions related to antimicrobials in adults admitted to an ICU in a 5-month period. The economic impact of pharmacist interventions was estimated considering difference in cost derived from antimicrobial treatment, adverse drug events and clinical pharmacist time. Results: A total of 212 drug related problems were detected in 114 patients, 18 being medication errors. Clinical pharmacist developed one intervention for each problem identified. 204 interventions (96.2%) were considered important with improved patient care and 7 (3.3%) very important. No negative impact of any intervention was identified. Physicians accepted 97.6% of the interventions. A potential saving of 10,905 € was estimated as a result of pharmacist interventions and 4.8 € were avoided per euro invested in a clinical pharmacist. Conclusions: A clinical pharmacist performing interventions on antimicrobials in the ICU has a positive impact on patient care and decreases costs.

Objective: Patients included in MAINRITSAN2 trial received either an individually tailored or a fixed-schedule therapy with rituximab as maintenance treatment of antineutrophil cytoplasm antibody associated vasculitides. The aim of this study was to compare the real-world costs of both arms. Method: We performed a cost-minimization analysis over an 18-month time period, estimating direct costs -drug acquisition, preparation, administration and monitoring costs- from the health system perspective. We conducted a number of additional sensitivity analyses with different assumptions for unit costs, with further scenarios including the interquartile range of the tailored-infusion group results, different number of monitoring visits for fixed-schedule regimen and different number of reported severe adverse events. A cost-effectiveness analysis was conducted as a sensitivity analysis using the absolute difference in the relapse rate and its confidence interval. Results: The individually tailored maintenance therapy with rituximab was shown to be a cost-saving treatment compared to the fixed-schedule therapy (6,049 euros vs. 7,850 euros). Savings resulted primarily from lower drug acquisition costs (2,861 vs. 4,768 euros) and lower preparation and administration costs (892 vs. 1,486 euros), due to the lower number of infusions per patient in the tailored-infusion regimen. The tailored-infusion regimen presented higher monitoring costs (2,296 vs. 1,596 euros). This result was replicated in all assumptions considered in the sensitivity analysis of cost-minimization approach. Conclusions: From the perspective of the health system, the tailored-therapy regimen seems to be the preferable option in terms of direct costs. Further studies assessing all the effects and costs associated to vasculitides maintenance treatment with rituximab are needed to support clinical management and healthcare planning.

The purpose of this paper was to review the literature regarding the clinical and economic impact of pharmacist interventions (PIs) related to antimicrobials in the hospital setting. A PubMed literature search from January 2003 to March 2016 was conducted using the terms pharmacist* or clinical pharmacist* combined with antimicrobial* or antibiotic* or anti-infective*. Comparative studies that assessed the clinical and/or economic impact of PIs on antimicrobials in the hospital setting were reviewed. Outcomes were classified as: treatment-related outcomes (TROs), clinical outcomes (COs), cost and microbiological outcomes (MOs). Acceptance of pharmacist recommendations by physicians was collected. PIs were grouped into patient-specific recommendations (PSRs), policy, and education. Studies' risk of bias was analyzed using Cochrane's tool. Twenty-three studies were evaluated. All of them had high risk of bias. The design in most cases was uncontrolled before and after. PSRs were included in every study; five also included policy and four education. Significant impact of PI was found in 14 of the 18 studies (77.8%) that evaluated costs, 15 of the 20 studies (75.0%) that assessed TROs, 12 of the 22 studies (54.5%) that analyzed COs, and one of the two studies (50.0%) that evaluated MOs. None of the studies found significant negative impact of PIs. It could not be concluded that adding other strategies to PSRs would improve results. Acceptance of recommendations varied from 70 to 97.5%. Pharmacists improve TROs and COs, and decrease costs. Additional research with a lower risk of bias is unlikely to change this conclusion. Future research should focus on identifying the most efficient interventions.

Background: Levetiracetam (LEV) is a second-generation antiepileptic drug extensively used in therapeutics. The aim of this study was to evaluate the influence that sex, age, and weight exert on LEV pharmacokinetics in clinical practice. Methods: We conducted a 6-year retrospective observational study. Patients were classified in subgroups according to sex, weight (normal range, overweight, and obese), and age (young adult: 16-30 years old, middle-aged adult: 31-50 years old, advanced adult: 51-64 years old, and elderly adult: >= 65 years old). We compared LEV apparent oral clearance (LEV CL/F) between the subgroups. Results: A total of 238 LEV basal serum concentrations (LEV C-0) corresponding to 156 patients were identified. Significant differences were observed in LEV CL/F between males and females when LEV CL/F was expressed as L/h [mean (SD): 4.79 (1.84) L/h in males versus 4.13 (1.64) L/h in females; P < 0.001]. These differences were not significant when LEV CL/F was normalized by weight [mean (SD): 60.64 (24.90) mL/h/kg in males versus 64.10 (28.87) mL/h/kg in females; n. s.]. Weight in females was 17% lower compared with males. A progressive reduction in LEV CL/F was observed with increasing age, in a proportion that was similar to the decline in renal function. The elderly patients presented 30% lower LEV CL/F (mL/h/kg) and 43% lower creatinine clearance (CCr) in comparison with adults. No statistically significant differences were observed in LEV CL/F calculated in L/h between weight subgroups. However, when LEV CL/F was expressed in mL/h/kg, a progressive reduction was observed [normal weight: 72.21 (28.97); overweight: 57.84 (25.38); obese: 49.45 (14.50); P < 0.001]. A significant and positive correlation between CCr and LEV CL/F was observed, confirming the important role of the renal function in LEV CL/F. The CCr increased in each sex group when weight increased; however, LEV CL/F (L/h) remained constant. Conclusions: Sex, age, and weight affect LEV pharmacokinetics, having an impact on the individual dosage regimen needed to achieve the therapeutic objective. Sex is a conditioning factor of LEV CL/F, although its influence is principally due to the weight. LEV CL/F decreases with advancing age, proportionally to the decline in renal function. It is confirmed that LEV dosage per body weight is not required, and prescribing higher doses of LEV in obese patients is not justified. These data suggest that routine LEV therapeutic drug monitoring in the elderly patients, patients with renal dysfunction, and obese patients is indicated.

The volume of health-care literature is growing at an increasing rate, with a huge amount of studies difficult to process. Therefore, we need tools or techniques to synthesize the information to help us in clinical decision-making. In fact, the available body of evidence ranges from single studies to umbrella reviews. In this scenario, evidence-based clinical decision-making requires knowing what type of evidence to use in every situation. However, a prerequisite for optimal decision-making is a greater understanding by professionals of the different techniques used to analyse their strengths, limitations and utilities. The purpose of this chapter is to take a journey from qualitative reviews to umbrella reviews. We start the tour on a fundamental point: term definitions, showing the variability among different authors. We go on to describe the differences, advantages, disadvantages and uses of different types of evidence, from individual studies to the `more specific methods¿ for knowledge synthesis, both qualitative and quantitative syntheses (systematic reviews, meta-analysis, network meta-analysis). Finally, in the last part of our journey, we compare the strengths and weaknesses of different evidence synthesis methods from the more traditional or specific to the more general or broader reviews (umbrella reviews, overviews of reviews, meta-epidemiologic reviews). Systematic reviews are at the top of the evidence pyramid. However, the number of systematic reviews published is increasing at a high rate, and decision-makers need to evaluate more evidence to answer their questions. Systematic reviews of existing systematic reviews, known as umbrella reviews, provide an overall examination of the body of information that is available for a given topic. Despite the limitations and weaknesses of tools to appraise and synthesize evidence, systematic reviews and umbrella reviews, including overviews of reviews and meta-epidemiological studies, continue to be the best tool for an approximation to the truth, in evidence-based terms.